Profiling metabolite changes in the neuronal differentiation of human striatal neural stem cells using ¹H-magnetic resonance spectroscopy

Objective: Neural stem cells (NSCs) have been found to play an increasing clinical role in stroke. However, at present, it is not yet possible to noninvasively monitor their differentiation once implanted into the brain. Methods: Here, we describe the use of high-resolution H-magnetic resonance spectroscopy (MRS) to define a metabolite profile of undifferentiated human striatal NSCs from the STROC05 cell line and their differentiation after 3-weeks of treatment with purmorphamine. Results: The undifferentiated conditions were characterized by ~95% of cells expressing nestin and ~77% being Ki67(+)ve, indicating that these were still proliferating. Phosphophocholine+glycerophosphocholine (PC+GPC) as well as myo-Inositol (mI) were increased in these cells. PC+GPC and mI were markedly reduced upon differentiation, potentially serving as markers of the NSC state. Upon differentiation (~45% neurons, ~30% astrocytes, ~13% oligodendrocytes), the concentration of many metabolites decreased in absolute value. The decreasing trend of the N-acetyl-aspartate level was observed in differentiated cells when compared with NSCs. An increase in plasmalogen (enriched in myelin sheets) could potentially serve as a marker of oligodendrocytes. Conclusion: These metabolite characteristics of undifferentiated and differentiated NSCs provide a basis for exploration of their possible use as markers of differentiation after cell transplantation.